Leg ulceration is the most prevalent chronic wound in Western countries, affecting about 1 to 2% of the adult population (Valencia I C, Falabella A, Kirsner R S, Eaglstein W H. Chronic venous insufficiency and venous leg ulceration. J Am Acad Dermatol 2001; 44: 401-21). The main causes of leg ulceration are venous hypertension, arterial insufficiency, and diabetes. Venous ulcers account for approximately 80% of all leg ulcers and are the result of venous hypertension. The current treatment for venous ulcers includes graduated compression support stockings or compression bandaging of the limb. Despite the standard of care of compression therapy, 50 to 70% of venous leg ulcers remain unhealed after 12 weeks of treatment and 54 to 78% of ulcers will reoccur (Abbade L P, Lastoria S. Venous ulcer:epidemiology, physiopathology, diagnosis and treatment. Int Wound J 2006; 3:113-20). These chronic wounds have a treatment cost in the United States of approximately one billion dollars per year and have a significant impact on the patient's quality of life (Herber O R, Schnepp W, Rieger M A. A systemic review on the impact of leg ulceration on patient's quality of life. Health Qual Life Outcomes 2007; 5: 44).
The biology of the chronic venous and diabetic wounds is quite different from acute wounds. In an acute wound the initial fibrin clot provides hemostasis and the platelets release cytokines, growth factors, and recruit inflammatory cells. The recruitment of inflammatory cells includes neutrophils and macrophages to eradicate bacteria. At the leading edge of the wound the protease cut through the fibrin clot. Matrix Metalloproteinases (MMP) are up regulated by the keratinocyte to cut a path through the matrix proteins to allow the keratinocyte to advance and close the wound. MMP-9 (gelatinase B) cuts through the basal lamina collagen (type IV) and anchoring collagen (type VII) to allow the keratinocytes to advance and close the wound. Once the keratinocytes cover the wound, the wound is re-epithelized, the basal lamina is reestablished and the MMP-9 is shut off.
However, in a chronic wound, the MMP-9 is not shut off. The elevated levels of this protease continue to destroy the wound matrix that is produced to heal the wound. The level of MMP-9 in a chronic wound can be five times of its level in an acute wound (Yager et al, 1996, Trengove et al, 1999). MMP-9 is the major protease that is present in the chronic venous stasis and decubitus ulcers.
The tissue inhibitor of metalloproteinase (TIMP-1) is absent from chronic wounds and is also decreased with age.
These chronic wounds also become colonized with bacteria. The bacterial colonies produce a biofilm which enables the bacteria to act as a multicellular organism. The biofilm protects the bacteria from the host immune system and all antibiotics. The bacterial biofilm gains nutrients from its own protease, which are similar to the host MMP-9. The biofilm then protects the bacteria from the host immune system and all antibiotics.
Thus, in chronic wounds, the bacterial biofilm and the host both produce proteases which are responsible for the degradation of the factors responsible for wound healing.
Current wound care products, including silver ointments and dressings, show no improvement in the healing rates of chronic venous or diabetic ulcers when used with compression therapy. (Palfreyman S, Nelson E A, Michaels J A. Dressings for venous leg ulcers: systemic review and meta-analysis. BMJ 2007; 335: 244).
There is a need to develop a new wound care treatment for chronic wounds that would decrease the socioeconomic impact of wound care and would improve healing rates.
The innovative proposed Improved Sock is comprised of a combination of silver nanoparticle (AgNP) shapes, natural wicking fibers, and elastic fibers composed into a yarn knitted to make the sock. The sock is applied directly on the wound with the natural wicking fibers with adhered AgNP shapes coming into contact with the wound. The Improved Sock directly down regulates the MMP-9 and bacterial proteases, kills the bacteria that is protected by the biofilm, and allows the epithelialization of the wound without harming the keratinocytes. The preferred natural wicking fibers are wool, such as merino wool, and/or alpaca.
Medical compression socks are known to increase the circulation in the feet and legs. The use of silver nanoparticles has proven to have antibacterial, antifungal and antiviral properties.
Currently, AgNPs have been used on textiles such as socks, clothing, and wound dressings. The AgNPs are either coated on the wound dressing or textile or they are incorporated into a polyester yarn, which is knitted with other fibers to create socks, clothing or wound dressing.
Current research shows that the AgNPs can be manufactured into specific shapes which show improved antibacterial properties (Pal, S., Y. K. Tak and J. M. Song, 2007, Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli. Appl. Environ. Microbiol. 2007, 73(6):1712). The AgNP shapes also demonstrate improved anti-inflammatory and angiogenic properties. The specific AgNP shapes which have shown improved antibacterial, anti-inflammatory, and angiogenic properties include silver nano prisms (AgNPr), silver nano truncated triangle plates (AgNTTP), and silver nano discs (AgND). Currently, a commercial product does not exist that combines the features of manufactured AgNP shapes (AgNPr, AgNTTP, AgND) with a compression sock made of natural fiber. The AgNP shapes allow for the use of a lower concentration of silver and results in a more effective wound care treatment. This new innovation will uniquely address the needs of patients with chronic wounds. The Improved Sock will increase circulation and will decrease the bacterial, fungal and viral loads that cause infections. This Improved Sock will also decrease the chronic inflammatory mediators which prevent wound healing and will stimulate wound healing by angiogenesis.